N3*

Modulators of the signal activity of the indolamina 2,3-dioxygenase and their therapeutic uses

Prof. Antonio Macchiarulo, University of Perugia; Prof. Ursula Grohmann, University of Perugia

University of Perugia

Challenge

Discovery of small molecular weight compounds that bind to the IDO1 enzyme and modulate its signaling function.

Technology

The invention concerns the discovery of a new class of small molecules with formula I that, by direct binding of IDO1, can activate IDO1-based signalling and consequent dendritic cell-mediated control of immunity over the long period. Among studied compounds, VIS-110 was selected as preclinical candidate being the most effective in both in vitro and in vivo pharmacological experiments. When administered in a multiple sclerosis disease model in mice (experimental autoimmune encephalomyelitis or EAE), VIS-110 was found to effectively reduce disease symptoms in a dose-dependent manner. Current treatment options against multiple sclerosis do not provide long-term protection against neurodegeneration, hence compounds such as VIS-110, which attempts modulation through novel pathways, could potentially be valuable alternatives.